Validity and completeness of registration of surgically treated malignant gynaecological diseases in the Danish National Hospital Registry.

BACKGROUND: The increasing tendency to acquire data by linkage to registries not designed for research has introduced a problem into epidemiological research. The data is often crude or possibly incomplete and, in some cases, it has been proposed to use these registries in the routine acquisition of data for existing epidemiological research registries. This study estimates the validity and completeness of the registration of surgically treated malignant gynaecological diseases in the Danish National Hospital Registry 1977-88. METHODS: Completeness was estimated by the method of independent case ascertainment, by comparison with the registration of surgically treated gynaecological cancer cases registered in the Danish Cancer Registry. The validity of the diagnoses was analysed by comparison with the recoding of discharge summaries describing the admission of a 5% random sample. RESULTS: The completeness of registration was 87% overall. Ovarian cancer, cervical cancer and cancer of the uterus were registered with a positive predictive value (PPV) of 89-90%. DISCUSSION: The results of the study emphasise the need to consider the validation of Danish Hospital Registry data before linkage and analysis. In epidemiological cancer research the Danish Cancer Registry is the better alternative when information on malignant tumours is needed.

[Occurrence of cancer in individuals with Down syndrome]. / Forekomsten af cancer hos personer med Downs syndrom.

Individuals with Down syndrome have an increased risk of leukaemia, but reliable estimates of the age-specific risk of leukaemia are lacking and very little is known about the risk of solid tumours. We identified 2814 individuals with Down syndrome from the Danish Cytogenetic Register, and linked the data to the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated on the basis of age- and sex-specific cancer rates in the general population. Sixty cases of cancer were observed, with 49.8 expected (SIR = 1.20; CI: 0.92-1.55). Leukaemia constituted 60% of the malignancies overall and 97% of the malignancies in children. The SIR for leukaemia varied considerably with age, being 56 (CI: 38-81) at age 0-4 years and 10 (CI: 4-20) at 5-29 years. No cases of leukaemia were observed after age 29. The cumulative risk of leukaemia by the age of 5 years was 2.1% and that by 30 years was 2.7%. Only 24 solid tumours were observed with 47.8 expected (SIR = 0.50; CI: 0.32-0.75). No cases of breast cancer were observed, with 7.3 expected (p = 0.0007). Increased risks of testicular cancer, ovarian cancer, and retinoblastoma were observed but were not statistically significant. The occurrence of cancer in Down syndrome is unique with a high risk of leukaemia in children and a decreased risk of solid tumours in all age groups. The distinctive pattern of malignancies may provide clues in the search for leukaemogenic genes and tumour suppressor genes on chromosome 21.

Risks of leukaemia and solid tumours in individuals with Down's syndrome.

BACKGROUND: Individuals with Down's syndrome have a greater risk of leukaemia than the general population, but reliable estimates of the age-specific risk are lacking and little is known about the risk of solid tumours. METHODS: We identified 2814 individuals with Down's syndrome from the Danish Cytogenetic Register, and linked the data to the Danish Cancer Registry. The number of person-years at risk was 48453. Standardised incidence ratio (SIR) and 95% CI were calculated of the basis of cancer rates specific for age and sex in the general population. FINDINGS: 60 cases of cancer were found, with 49.8 expected (SIR 1.20 [95% CI 0.92-1.55]). Leukaemia constituted 60% of cases of malignant disease overall and 97% of cases in children. The SIR for leukaemia varied with age, being 56 (38-81) at age 0-4 years and 10 (4-20) at 5-29 years. No cases of leukaemia were seen after the age of 29 years. The SIR for acute myeloid leukaemia was 3.8 (1.7-8.4) times higher than that for acute lymphoblastic leukaemia in children aged 0-4 years. The cumulative risk for leukaemia by the age of 5 years was 2.1% and that by 30 years was 2.7%. Only 24 solid tumours were seen, with 47.8 expected (0.50 [0.32-0.75]). No cases of breast cancer were found, with 7.3 expected (p=0.0007). Higher than expected numbers of testicular cancers, ovarian cancers, and retinoblastomas were seen but were not significant. INTREPRETATION: The occurrence of cancer in Down's syndrome is unique with a high risk of leukaemia in children and a decreased risk of solid tumours in all age-groups. The distinctive pattern of malignant diseases may provide clues in the search for leukaemogenic genes and tumour-suppressor genes on chromosome 21.

[Incidence of cancer in individuals with Down syndrome]. / Forekomsten af cancer hos personer med Downs syndrom.

Individuals with Down syndrome have an increased risk of leukaemia, but reliable estimates of the age-specific risk of leukaemia are lacking and very little is known about the risk of solid tumours. We identified 2814 individuals with Down syndrome from the Danish Cytogenetic Register, and linked the data to the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated on the basis of age- and sex-specific cancer rates in the general population. Sixty cases of cancer were observed, with 49.8 expected (SIR = 1.20; CI: 0.92-1.55). Leukaemia constituted 60% of the malignancies overall and 97% of the malignancies in children. The SIR for leukaemia varied considerably with age, being 56 (CI: 38-81) at age 0-4 years and 10 (CI: 4-20) at 5-29 years. No cases of leukaemia were observed after age 29. The cumulative risk of leukaemia by the age of 5 years was 2.1% and that by 30 years was 2.7%. Only 24 solid tumours were observed with 47.8 expected (SIR = 0.50; CI: 0.32-0.75). No cases of breast cancer were observed, with 7.3 expected (p = 0.0007). Increased risks of testicular cancer, ovarian cancer, and retinoblastoma were observed but were not statistically significant. The occurrence of cancer in Down syndrome is unique with a high risk of leukaemia in children and a decreased risk of solid tumours in all age groups. The distinctive pattern of malignancies may provide clues in the search for leukaemogenic genes and tumour suppressor genes on chromosome 21.

The Danish Cancer Registry--history, content, quality and use.

The Danish Cancer Registry is a population-based registry containing data on the incidence of cancer throughout Denmark since 1943. Reporting of cancer was made mandatory by administrative order in 1987. Details of individual cases of cancer are available according to the 7th revision of the International Classification of Diseases (ICD) for all years, and according to the ICD-O since 1978. A core data set is kept on each individual which includes date of birth, sex, date of cancer diagnosis, method of verification, date of death and cause of death. This paper describes the history of the registry, its data sources and its procedures, including quality control and access to data. Integration of both research activities and registration since the inception of the Registry has maintained the completeness and validity of the data for 1943-1996.

Survival of Danish cancer patients 1943-1987. Lymphatic and haematopoietic tissues.

In Denmark, 6.6% of all malignant neoplasms among men and 5.5% among women occur in the lymphatic and haematopoietic tissues. Most are generalized when diagnosed, although lymphomas are sometimes confirmed to one region. Treatment has been predominantly by chemotherapy since the 1960s, and is often combined with radiation for lymphomas and myeloma. The five-year survival rates for non-Hodgkin's lymphoma improved by 20% between 1970 and 1987. An improvement in survival from Hodgkin's disease began earlier, with a relative five-year survival rate of about 30% in 1960 and of 72% in 1983-87. Survival was better for younger patients (< 50 years) with stage I-II disease, the relative five-year survival rates being 83-93% in 1983-87. For cases of leukaemia much of the improvement in survival rates was founded in 1960s on success in the treatment of childhood leukaemia (acute lymphatic leukaemia); the relative five-year survival rates for children under 10 years of age increased from 12% to 75-80%. Smaller improvements were seen in survival from other types of leukaemia, including the chronic forms. Thus, even for chronic lymphocytic leukaemia, which has a favourable prognosis but is regarded as incurable, improvements in survival rates were seen, which may be attributed to chemotherapeutic treatment or earlier diagnosis. It was not surprising that the dramatic improvement in survival rates coincided with the introduction of chemotherapeutic treatment regimes, as reported previously in clinical series. Acute and chronic cytotoxic side-effects are of concern, and, since both cytotoxic drugs and radiation are potent carcinogens, second primary cancers have been reported to be induced by treatment of cancers (Storm & Prener, 1985). The improvements in the survival rates for the haematopoietic malignancies, however, outweigh the de novo cancer risk related to therapy.

Supravaginal uterine amputation in Denmark 1978-1988 and risk of cancer.

In Denmark, total rather than subtotal hysterectomy has been recommended as treatment for benign conditions of the uterine corpus, primarily due to the risk of cervical cancer in the residual stump. Due to possible benefits during and after surgery, it has recently been argued that total hysterectomy for benign conditions could be substituted by subtotal hysterectomy, particularly since cancers of the cervix are declining as a consequence of screening. Cancer risk following supravaginal uterine amputation among 1104 Danish women undergoing operations during 1978-1988 was studied using record linkage techniques with the Danish Cancer Registry. No overall cancer risk, nor an overall increased risk of cancers coded as cervical, was observed. However, a 3.3 to 5.0-fold increased risk for cervical cancer was observed among women whose operations occurred at 50 years of age or older, possibly reflecting an increased risk of cancer in the endocervical area or in remaining uterine tissue. This observation, together with the difficulties in treating a cervical cancer of the stump when it does occur, should be taken into account before a change in surgical procedures from total to subtotal hysterectomies is recommended.

Bambuterol: clinical effects of three doses of bambuterol once daily in asthmatic patients.

Twenty-two asthmatics received bambuterol solution, a terbutaline pro-drug, once every evening. The following doses were each given orally for 7 days in a double-blind cross-over study: 0.185, 0.270 and 0.400 mg/kg. Bambuterol 0.270 mg/kg was preferable regarding clinical effects and side effects. The plasma concentration of generated terbutaline showed a slow linear decrease at all doses. Tests of two methods for objective measurements of tremor in five patients did not add any new data compared with the subjective recordings.

Bambuterol: clinical effects of different doses of a long-acting bronchodilator prodrug.

Sixty-eight asthmatics participated in a dose-finding study on bambuterol, a terbutaline prodrug, administered once every evening. Bambuterol administrations of 0.185, 0.270 and 0.400 mg/kg gave effective and long-lasting bronchodilation, for at least 24 h, with the two higher doses probably close to the maximal effect of the drug. Bambuterol 0.400 mg/kg was associated with more adverse effects than bambuterol 0.185 mg/kg. The side effects were those expected in oral beta 2-agonist treatment and mainly experienced by patients who had not been on oral beta 2-agonists before. The most favourable of the investigated doses was found to be 0.270 mg/kg. It can not be excluded, however, that a somewhat lower dose may still be as beneficial. This will be investigated in forthcoming studies.

Baseline and interferon-enhanced natural killer cell activity in rheumatoid arthritis.

Natural killer (NK) cell activity against the leukemia cell line K-562 was tested in 45 patients with rheumatoid arthritis (RA) who either had not received any remission-inducing drugs for more than 6 months or had received penicillamine for at least 6 months. Baseline NK cell activity and interferon (IF)-enhanced NK cell activity did not differ from that observed in 45 controls matched for age and sex, and neither NSAID (non steroidal anti-inflammatory drugs) nor penicillamine influenced NK cell activity. There was no correlation between NK cell activity and acute-phase reactants.

High-dose survival in the lymphocytic choriomeningitis virus infection is accompanied by suppressed DTH but unaffected T-cell cytotoxicity.

Provided that intracerebral inoculation is applied, an increase in the virus dose from 10(2) to 10(4) LD50 of lymphocytic choriomeningitis virus (LCMV) leads to strikingly reduced mortality. To analyse the background for this autointerference, we measured several virologic and immunologic variables in mice infected with these doses of virus. In the high-dose mice we found generally higher organ virus titres and serum interferon titres than in the low-dose mice. Since we could demonstrate that virus-specific T-cell cytotoxicity in spleen, peripheral blood, and meningeal exudate was similar after intracerebral infection with large and small virus doses, and since the LCMV infection in the brain qualitatively and quantitatively was independent of the size of virus inoculum, the explanation for the survival of the high-dose animals is obviously not lack of possibilities for interaction between cytotoxic T cells and infected sensitive targets in the central nervous system. On the other hand, high doses of virus caused a clear suppression of the LCMV-specific delayed-type hypersensitivity (DTH). In addition, when splenocytes from high-dose animals were transferred either intravenously or locally into the footpad of newly virus-challenged mice, DTH was markedly suppressed as compared with the response after transfer of spleen cells from low-dose mice. We therefore conclude that autointerference in the LCMV infection is due to a selective suppression of Td function. Large amounts of persistent virus late after infection with high doses of virus suggest a central role for Td function also in virus clearance. Finally, our results indicate the existence of two subsets of K,D region-restricted T cells, one mediating cytotoxicity and the other mediating DTH. This possibility is discussed.